From a fascinating paper in Modern Pathology:
21 paraffin-embedded lung biopsies from patients diagnosed with idiopathic pulmonary fibrosis and 21 lung biopsies from age-matched controls with pulmonary fibrosis of known etiology were examined for a series of γ−herpesviruses’ DNA/RNA and related proteins using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods. We detected four proteins known to be in the genome of several γ−herpesviruses (cyclin D, thymidylate synthase, dihydrofolate reductase, and interleukin-17) that were strongly co-expressed in the regenerating epithelial cells of each of the 21 idiopathic pulmonary fibrosis cases and not in the benign epithelia of the controls. Among the γ−herpesviruses, only herpesvirus saimiri expresses all four of these ‘pirated’ mammalian proteins. We found herpesvirus saimiri DNA in the regenerating epithelial cells of 21/21 idiopathic pulmonary fibrosis cases using four separate probe sets but not in the 21 controls. RT-PCR showed that the source of the cyclin D RNA in active idiopathic pulmonary fibrosis was herpesvirus saimiri and not human. We cloned and sequenced part of genome corresponding to the DNA polymerase herpesvirus saimiri gene from an idiopathic pulmonary fibrosis sample and it matched 100% with the published viral sequence. These data are consistent with idiopathic pulmonary fibrosis representing herpesvirus saimiri-induced pulmonary fibrosis.
Via PulmCCM.
From a recent study:
Background—Patients with heart failure (HF) are typically designated as having reduced or preserved ejection fraction (HFREF, HFPEF) because of the importance of left ventricular ejection fraction (LVEF) on therapeutic decisions and prognosis. Such designations are not necessarily static, yet few data exist to describe the natural history of LVEF over time.
Methods and Results—We identified 2413 patients from Kaiser Permanente Colorado with a primary discharge diagnosis of HF between January 1, 2001, and December 31, 2008, who had greater than or equal to 2 LVEF measurements separated by greater than or equal to 30 days. We used multi-state Markov modeling to examine transitions among HFREF, HFPEF, and death. We observed a total of 8183 transitions. Women were more likely than men to transition from HFREF to HFPEF (hazard ratio, 1.85; 95% confidence interval, 1.38–2.47). Patients who were adherent to β-blockers were more likely to transition from HFREF to HFPEF (hazard ratio, 1.53; 95% confidence interval, 1.10–2.13) compared with patients who were nonadherent to β-blockers, whereas angiotensin-converting enzyme or angiotensin II receptor blocker adherence was not associated with LVEF transitions. Patients who had a previous myocardial infarction were more likely to transition from HFPEF to HFREF (hazard ratio, 1.75; 95% confidence interval, 1.26–2.42).
Conclusions—In this cohort of patients with HF, LVEF is a dynamic factor related to sex, coexisting conditions, and drug therapy. These findings have implications for left ventricular systolic function ascertainment in patients with HF and support evidence-based therapy use, especially β-blockers.
Again, it bears repeating that beta blocker use is associated with improvement in EF whereas ACEI and ARB use are not. Note that ACEIs and ARBs, but not beta blockers, are part of the heart failure performance measures.
It proved effective in this study of patients at renal risk undergoing coronary angiography:
Contrast medium–induced acute kidney injury occurred in 26 patients (26%), 20 (40%) in the control group and 6 (12%) in the remote ischemic preconditioning group (odds ratio, 0.21; 95% confidence interval, 0.07–0.57; P=0.002). No major adverse events were related to remote ischemic preconditioning.
Despite the fact that this was published a year and a half ago it hasn't made prime time as far as I can tell. Imagine doing this to a patient:
IPC was accomplished by performing 4 cycles of alternating 5-minute inflation and 5-minute deflation of a standard upper-arm blood pressure cuff to the individual's systolic blood pressure plus 50 mm Hg to induce transient and repetitive arm ischemia and reperfusion. IPC was started immediately before CA.
From a recent paper:
Methods A retrospective time-series segmented regression analysis was conducted in a tertiary centre from January 2001 to December 2011. Ertapenem was introduced in January 2005...
Results Mean monthly use of imipenem was 2.9 ± 0.9 DDDs/100 PDs, as compared with 1.2 ± 0.7 DDDs/100 PDs for meropenem and 1.0 ± 0.7 DDDs/100 PDs for ertapenem (after its introduction). After ertapenem adoption, a downward trend was seen in the use of imipenem (P = 0.016) and ciprofloxacin (P = 0.004). A total of 6272 Pseudomonas aeruginosa and 1093 A. baumannii isolates were evaluated. Susceptibility of P. aeruginosa to imipenem improved after ertapenem introduction, both according to the proportion of susceptible isolates (P = 0.002) and to the incidence density of resistance (P less than or equal to 0.001). No significant change was seen in A. baumannii susceptibility to imipenem (P = 0.772). By multiple linear regression analysis, the incidence density of imipenem-resistant P. aeruginosa increased with the use of imipenem (P = 0.003) and ciprofloxacin (P = 0.008). Occurrence of outbreaks (P less than or equal to 0.001) and use of gentamicin (P = 0.007) were associated with A. baumannii resistance to imipenem.
Conclusions Use of ertapenem was directly associated with a downward trend in the use of imipenem and ciprofloxacin, which may have contributed to improve the susceptibility of P. aeruginosa to imipenem. Ertapenem use had no impact on the susceptibility of A. baumannii to imipenem.
Via Hospital Medicine Virtual Journal Club.
A review of octreotide recently appeared in Chest.
Octreotide is a synthetic analogue of somatostatin. An understanding of the biologic and pharmacologic principles surrounding this agent is important, as it has recently seen increasing use for a diversity of indications in hospitalized patients. Following are a few points of interest from the review.
Somatostatin (SST) is a hypothalamic hormone best known for its inhibition of growth hormone secretion. However, it has other actions less well appreciated. For example, from the review:
SST is synthesized not only in the hypothalamus but also by δ cells of the pancreatic islets, the myenteric neural plexi, and the epithelial lining of the stomach and intestines. Based on the sites where it is found, it is not surprising that SST can influence numerous endocrine and exocrine functions of the GI tract and pancreas, including inhibition of the secretion of insulin, glucagon, cholecystokinin, gastrin, secretin, serotonin, vasoactive intestinal peptide, motilin, and pancreatic polypeptide.3,4 Thus, SST and its synthetic analogs are able to inhibit gastric acid production, gastric emptying, and GI motility, pancreatic exocrine and endocrine secretion, nutrient absorption (eg, glucose, fats, amino acids), and biliary flow and contractility. These functional effects of SST provide the rationale for the use of SST analogs in various GI and non-GI endocrine disorders such as carcinoid syndrome, islet cell tumors, β-islet cell hyperplasia (nesidioblastosis), and acromegaly.4,5 In addition, SST and octreotide can induce vasoconstriction of the splanchnic vessels, thereby reducing blood flow in the splanchnic and portal venous systems.3,4
Clinical uses in hospitalized patients:
Variceal bleeding
Octreotide induces splanchnic vasoconstriction which reduces splanchnic flow thereby reducing portal venous pressure.
Hepatorenal syndrome
The splanchnic vasodilation characteristic of cirrhosis reduces effective blood volume in turn activating a neurohumoral response. These factors are adverse to renal perfusion. By inducing splanchnic vasoconstriction octreotide may help reverse these effects. However, it is not effective as monotherapy and for treatment of HRS is combined with another vasoconstrictor, typically midodrine. The level of supporting evidence is low.
Hypoglycemia from sulfonylureas
The hypoglycemia associated with sulfonylurea therapy can be profound and prolonged. Glucose therapy is necessary as part of the treatment but when used alone may associated with rebound hypoglycemia since sulfonylurea agents are insulin secretagogues and a glucose load stimulates insulin release. Octreotide is a useful adjunct and is now favored over glucagon for sulfonylurea induced hypoglycemia.
Chylous pleural effusion
Octreotide reduces intestinal chyle production thus improving the chances for resolution.
It can be as bad as Alzheimer's according to this study by Vanderbilt researchers.
There's an interesting discussion of the paper at PulmCCM.
Sepsis guidelines recommend initiation of enteral nutrition in lower amounts than recommended by nutrition guidelines. This paper suggests that initial rates of EN closer to the nutrition guideline recommendations are associated with better outcomes.
HT to Hospital Medicine Virtual Journal Club.
Here's a primer for physicians. From the article:
Physicians who accept payment from the federal health-care programs, most notably Medicare and Medicaid, face a bewildering array of requirements that grow more complex each year...
Many fraud prohibitions are clear, yet others encompass activities that might appear to be innocuous, cost-effective, or even beneficial...
The Health Insurance Portability and Accountability Act of 1996 (HIPAA) brought major changes to fraud enforcement.1 In addition to defining new federal crimes, most notably federal Health-care Fraud, HIPAA directed more funds to the US Department of Health and Human Services (DHHS) and Department of Justice to combat health-care fraud...
Plain language summary:
The government is continually inventing crimes for doctors and spending more and more money in the process. The resulting regulatory environment lacks clarity and is next to impossible to navigate, but here's an attempt to help.
A recent report from MMWR:
Symptomatic infection of the heart is rare in recognized Lyme disease cases and usually resolves promptly with appropriate antibiotic therapy. Nonetheless, cardiac involvement occasionally can cause life-threatening cardiac conduction abnormalities. During November 2012–July 2013, one woman and two men (ranging in age from 26 to 38 years) from high-incidence Lyme disease states experienced sudden cardiac death and, on postmortem examination, were found to have evidence of Lyme carditis.
This represents a higher frequency than what has been reported before. These individuals had no prior history or extracardiac manifestations of Lyme disease.
From an associated Medscape article:
"The Borrelia burgdorferi spirochetes actually make it into the heart tissue. Whether the resulting carditis is due to the spirochetes themselves or to the immune responses to them or to a combination of both is unclear," Dr. Forrester said.
The most common manifestation of Lyme carditis is atrioventricular (AV) conduction blockade. Dr. Forrester said that sudden cardiac death might be the result of the conduction abnormality leading to fatal arrhythmia...
"The current article further reiterates the importance of identification of Lyme carditis as a cause of heart block. I think this is more relevant to primary care physicians who manage the patients at the front end. The diagnosis of Lyme carditis can be challenging if it is the initial presentation of the disease process and [the] patient does not remember having a tick bite. AV block may be the first and only sign of Lyme disease," said Paras Karmacharya, MD...
"Although more than 90% of patients with Lyme carditis have complete recovery, patients with more severe conduction system disturbances (first-degree AV block with a PR interval greater than 0.3 seconds, second- or third-degree AV block) should be referred immediately to the emergency department and hospitalized in a coronary care unit for treatment with intravenous antibiotics like ceftriaxone or high-dose penicillin G. Insertion of a temporary transvenous pacemaker may be required. As in the case described in our article, the degree of heart block can fluctuate from first degree to second degree to complete AV block very quickly in minutes to hours, so careful observation is prudent. Treatment with an antibiotic can revert the AV block within 48 hours of therapy, so identification of this potentially reversible cause of heart blocks may help prevent significant morbidity and mortality," Dr. Karmacharya said.
"Once you start treatment for Lyme carditis, the prognosis is excellent," Dr. Forrester emphasized.
Here is a free full text review.
Listed among the contraindications to NIPPV in this and other reviews is impaired level of consciousness. However, its use in hypercapnic RF with decreased LOC is common. Concerning that, the review says:
Patients with altered levels of consciousness due to hypercapnic ARF associated with COPD exacerbation are exposed to high risk of NIV failure, but a cautious attempt with NIV may be performed in these patients, provided that a careful monitoring is available and prompt ETI is accessible [31]. In treatment-responsive patients, recovery of consciousness occurs within 45–60 min after NIV application.
From a recent review:
Maintenance treatment with low-dose macrolides such as erythromycin and azithromycin provides clinical benefit in several chronic neutrophilic airway diseases, including cystic fibrosis (CF), non-CF bronchiectasis and exacerbation-prone chronic obstructive pulmonary disease. Although several short-term studies of macrolides in mild-to-moderate asthma have failed to improve lung function, the AzIthromycin in Severe Asthma trial has demonstrated a significant reduction in the rate of exacerbations in patients with exacerbation-prone noneosinophilic severe asthma. As chronic macrolide use is associated with the risks of population antimicrobial resistance, this add-on treatment should be restricted to severe asthma patients at greatest unmet need despite optimal asthma management.
Recent thinking concerning digoxin is that when used adjunctively in patients with systolic heart failure it reduces hospitalizations and can increase or have a neutral effect on mortality depending on achieved serum levels. This thinking is challenged by a new study:
Methods and Results—We identified adults with incident systolic HF between 2006 and 2008 within Kaiser Permanente Northern California who had no prior digoxin use. We used multivariable extended Cox regression to examine the association between new digoxin use and risks of death and HF hospitalization, controlling for medical history, laboratory results, medications, HF disease severity, and the propensity for digoxin use. We also conducted analyses stratified by sex and concurrent β-blocker use. Among 2891 newly diagnosed patients with systolic HF, 529 (18%) received digoxin. During a median 2.5 years of follow-up, incident digoxin use was associated with higher rates of death (14.2 versus 11.3 per 100 person-years) and HF hospitalization (28.2 versus 24.4 per 100 person-years). In multivariable analysis, incident digoxin use was associated with higher mortality (hazard ratio, 1.72; 95% confidence interval, 1.25–2.36) but no significant difference in the risk of HF hospitalization (hazard ratio, 1.05; 95% confidence interval, 0.82–1.34).
This study found a negative effect:
Methods This pre-post cohort design enrolled 75 patient-nurse-physician triads prior to the introduction of EMR, and 123 triads after the introduction of EMR. Nurses and patients reported whether they communicated with the physician that day. Patients, nurses and physicians answered several questions about the plan of care for the day. Responses were scored for degree of agreement and compared between pre-EMR and post-EMR cohorts. The primary outcome was Total Agreement Score, calculated as the sum of the agreement responses. Chart review was performed to determine patients’ actual length of stay.
Results Although there was no difference between the frequency of nurses reporting communication with physicians before and after EMR, face-to-face communication was significantly reduced (67% vs 51%, p=0.03). Total Agreement Score was significantly lower after the implementation of EMR (p=0.03). Additionally, fewer patients accurately predicted their expected length of stay after EMR (34% vs 26%, p=0.001).
Conclusions The implementation of EMR was associated with a decrease in face-to-face communication between physicians and nurses, and worsened overall agreement about the plan of care.
Via Hospital Medicine Virtual Journal Club.
This discussion is primarily on the renal aspects, along with some general comments about IgG 4 related conditions as systemic diseases.
Is there a significant interaction? A disulfiram-like reaction has been long purported and is mentioned in the product labeling for metronidazole. How important it is and whether it even exists at all, however, are matters of debate. Here is a nice topic rundown with literature citations at Emergency Medicine Pharm D.
Here is a recent NEJM review.
There is a paucity of high level evidence to guide clinicians due to the rarity of the condition. However advances in critical care and transplantation have improved the outlook. The authors' recommendations are based largely on expert opinion and lower level evidence.
Definition
The designation acute liver failure (ALF) has largely replaced the old phrase fulminant hepatic failure. The general definition remains the same:
..defined as “a severe liver injury, potentially reversible in nature and with onset of hepatic encephalopathy within 8 weeks of the first symptoms in the absence of pre-existing liver disease..
Subcategories have been proposed, listed in the article, based on time from symptom onset to fully developed ALF. These time intervals provide clues as to etiology.
Etiology
Viral---mainly hep A and E. In addition hep B can be a sleeping giant awakened by immunosuppressive drugs.
Drugs---account for about half of cases in the U.S. Acetaminophen is the most common of these and indeed the most common cause of ALF overall in the U.S. For acetaminophen it's dose related toxicity (subacute worse than a single overdose) but for the other drugs it's idiosyncratic (rare).
Other---ischemic, Budd-Chiari, pregnancy related, miscellaneous, unknown.
Management aspects
Acetylcysteine may be helpful even in patients with non-acetaminophen induced ALF.
Avoidance of hypoglycemia.
Avoidance of hyponatremia (the article recommends maintaining Na on the high side and specifies an optimal range).
Aggressive indications for intubation and mechanical ventilation in patients with encephalopathy (the article specifies an optimal PCO2 range). This is mainly for neuro and airway management though aspiration and ARDS are known complications of ALF.
Preemptive antibiotics (the patients are at high infection risk, and manifestations of ALF often mimic, mask or overlap those of sepsis).
A different profile of encephalopathy compared to that of end stage chronic liver disease
---in which cerebral edema dominates the picture to a greater extent. This is due in large part to the rapidity of ammonia rise in ALF as compared to end stage chronic liver disease. This outpaces the brain's ability to marshal its defenses against swelling.
Dialysis for the liver???
For now extracorporeal treatment modalities are restricted to the setting of clinical trials.
A series of educational videos on numerous medical topics.
This report from the CDC's MMWR contains a world of information. It is available as free full text.
Key points:
This, the worst flu season since the 2009 pandemic, represents a resurgence of novel pandemic 2009 H1N1 influenza (pH1N1). All of the severe (ICU admission) and fatal cases that were subtyped proved to be pH1N1.
Rapid influenza tests had low sensitivity. 42% false negative rate with PCR as the standard.
Risk factors for severe disease included lack of vaccination, medical comorbidities and obesity.
The report includes recommendations for anti-viral therapy:
Approximately 54% of hospitalized patients with fatal illness did not receive antiviral treatment at hospital presentation. Neuraminidase inhibitors have an excellent safety profile and empiric treatment with a neuraminidase inhibitor should be initiated as soon as possible for any hospitalized patient with suspected influenza (8). For outpatients with high-risk conditions and persons with progressive disease who are not being admitted, antiviral treatment is also recommended (9).¶ Observational studies have also reported modest clinical benefits when antiviral treatment is started late in the course of illness, which indicates that even patients admitted late in the course of illness should receive antiviral treatment (10). Either oral oseltamivir or inhaled zanamivir are recommended for treatment of suspected or confirmed influenza (http://www.cdc.gov/flu/professionals/antivirals/summary-clinicians.htm). Inhaled zanamivir should not be used for patients who are severely ill with influenza or intubated. For severely ill patients with influenza who cannot receive oral oseltamivir or inhaled zanamivir, intravenous zanamivir, an investigational drug, can be considered.** Oseltamivir resistance is low among circulating influenza viruses in the United States.
HT to Hospital Medicine Virtual Journal Club.
What a horrible job we're doing:
The aim of this study was to determine patient characteristics, indications for IVCF placement, retrieval rates, complications, and post-IVCF anticoagulation (AC) practices in patients who have received IVCFs. A retrospective review of IVCF use by 3 specialty groups from January 1, 2009, to December 31, 2011, was conducted at a tertiary referral center...Indications for IVCF placement included contraindication to AC in the presence of acute venous thromboembolism (n = 287 [41.7%]) and prophylaxis (n = 235 [34.2%]). Insertion-related complications occurred in 28 patients (4.1%). After IVCF placement, adequate AC was initiated in 454 patients (66.0%) less than 3.0 days (interquartile range 0 to 13.0) after insertion, but the overall retrieval rate was only 252 of 688 (36.6%)...many patients have IVCF-related complications, and often, even when IVCFs are retrieved, there is a delay between AC and retrieval. Quality improvement initiatives that facilitate the expeditious retrieval of IVCF are needed.
This isn't the first time I've been made aware that removal rates for retrievable filters are low. It's almost funny that we would have to consider a “systems” initiative for something so simple and so obvious. How can the hospitalist help? In consulting someone to insert an IVC filter discuss the indications for a retrievable versus a permanent filter. If a retrievable one is used discuss the plans for removal, early. Inform the patient. Be explicit about it in the medical record.
These investigators noted positive serology in health care workers exposed to patients hospitalized with Pneumocystis jirovecii (formerly known as PCP). The concern is that these individuals (who don't become ill because they're immunocompetent) could transmit the disease to immunocompromised patients. Such a transmission sequence has been demonstrated in mice. Whether these findings warrant a change in infection control policies in hospitals is unknown.
Free full text review here.
This formula is the one I mentioned here, to help differentiate subtle anterior STEMI changes from normal variant anterior ST elevations and early repolarization. In a recent post Dr. Smith provides a link to his original paper which reported the formula.
---in this study. Key points from the article:
•AKI progresses in about 50% of septic patients despite hemodynamic optimization.
•We observed a weak association between systemic hemodynamic parameters and AKI in septic patients.
•Higher mean CVP in the first 24 hours was linearly associated with increasing risk of new or persistent AKI across all observed CVP values.
•The association of elevated CVP with AKI suggests a role of venous congestion in the development of AKI.
•The paradigm that targeting high CVP may reduce the occurrence of AKI should be revised.
These findings raise many questions. If we restrict volume to spare the kidneys do we under-resuscitate the rest of the body? What if we pour it on initially then cut back after 6 hours (early goal directed therapy)?
What about non gap acidosis??
It's HARDUP.
This study looked at 1001 septic patients and compared attributes and outcomes between the culture positive and culture negative groups:
There were 415 culture-negative patients (41.5%) and 586 culture-positive patients (58.5%). Gram-positive bacteria were isolated in 257 patients, and gram-negative bacteria in 390 patients. Culture-negative patients were more often women and had fewer comorbidities, less tachycardia, higher blood pressure, lower procalcitonin levels, lower Acute Physiology and Chronic Health Evaluation II [median 25.0 (interquartile range 19.0-32.0) versus 27.0 (21.0-33.0), P = 0.001] and Sequential Organ Failure Assessment scores, less cardiovascular, central nervous system, and coagulation failures, and less need for vasoactive agents than culture-positive patients. The lungs were a more common site of infection, while urinary tract, soft tissue and skin infections, infective endocarditis and primary bacteremia were less common, in culture-negative than in culture-positive patients. Culture-negative patients had a shorter duration of hospital stay [12 days (7.0-21.0) versus 15.0 (7.0-27.0), P = 0.02] and lower ICU mortality than culture-positive patients. Hospital mortality was lower in the culture-negative group (35.9%) than in the culture-positive group (44.0%, P = 0.01), the culture-positive subgroup which received early appropriate antibiotics (41.9%, P = 0.11), and the culture-positive subgroup which did not (55.5%, P less than 0.001). After adjusting for covariates, culture positivity was not independently associated with mortality on multivariable analysis.
Not approved yet but probably soon will be based on this study.
These are some teaching points from a talk given by Lindy P. Fox, MD at UCSF's 17th annual hospital medicine course.
Morbilliform rash versus drug hypersensitivity (aka DRESS or DIHS). [1] [2]
Morbilliform means “looks like measles.” No systemic symptoms. Benign.
The much more serious (mortality up to 25%) hypersensitivity syndrome is characterized by:
Later onset (2-6 weeks after drug start, time for abnormal metabolites to accumulate).
Systemic symptoms and signs (fever precedes rash).
Multiorgan involvement (pattern may vary according to the culprit drug).
Possible role for HHV6 in drug hypersensitivity syndrome (consider checking PCR).
Hepatitis resolution signals recovery.
Manifest cardiac involvement (DCM) may be late.
Rx (in addition to drug discontinuation and avoidance of cross reacting drugs) is systemic steroids and other immunomodulating agents may be necessary.
Stevens Johnson syndrome and toxic epidermal necrolysis
On an overlapping spectrum distinguished by degree of body surface involvement and the presence of spotty versus confluent lesions.
Etiology: drugs (maybe mycoplasma and HSV in some cases of SJS).
Ocular damage a concern. Get ophthalmology consult.
Rx: in additional to general supportive and burn care, systemic steroids for SJS, IVIG for TEN.
What distinguishes Norwegian scabes?
Hyperkaratotic, crusted lesions, huge mite burden.
Elderly, frail, immunocompromised, institutionalized.
High mortality (due to underlying condition and secondary infection, typically staph).
Can lead to erythroderma, multiple complications, failure to thrive.
Rx aggressive topical and sometimes systemic.
See these links [3] [4]
Pustular psoriasis, a dermatology emergency
Precipitated when a psoriatic is placed on steroids then tapered.
May have life threatening systemic manifestations (fever, high cardiac output state, electrolyte imbalances).
Image here.
Pyoderma gangrenosum
Rapidly progressive ulceration.
Precipitated by trauma (eg surgical).
50% have an underlying predisposing condition (inflammatory bowel, heme malignancy, others).
Debridement makes it worse.
Rx steroids, topical + systemic. Other immunomodulators may be necessary.
Image here.
A systematic review and guideline from the American College of Physicians. Free full text.
---in this study:
Methods
We investigated the effects of weight gain on adipocyte size, macrophage influx, and mRNA expression and protein levels of key inflammatory markers within the adipose tissue in patients with type 2 diabetes mellitus before and 6 months after starting insulin therapy.
Results
As expected, insulin therapy significantly increased body weight. At the level of the subcutaneous adipose tissue, insulin treatment led to an influx of macrophages. When comparing patients gaining no or little weight with patients gaining greater than 4% body weight after 6 months of insulin therapy, both subgroups displayed an increase in macrophage influx. However, individuals who had gained weight had higher protein levels of monocyte chemoattractant protein-1, TNF-α and IL-1β after 6 months of insulin therapy compared with those who had not gained weight.
Conclusions/interpretation
We conclude that insulin therapy in patients with type 2 diabetes mellitus improved glycaemic control but also induced body weight gain and an influx of macrophages into the subcutaneous adipose tissue. In patients characterised by a pronounced insulin-associated weight gain, the influx of macrophages into the adipose tissue was accompanied by a more pronounced inflammatory status.
Little wonder that many glucose lowering pharmacologic therapies in DM 2 have been associated with macrovascular harm.
From a survey published in BMC Anesthesiology:
Results
Over half of patients (57%) agreed that pre-existing DNR requests should be suspended while undergoing a surgical procedure under anesthesia, but 92% believed a discussion between the doctor and patient regarding perioperative resuscitation plans should still occur. Thirty percent of doctors completing the survey believed that DNR orders should automatically be suspended intraoperatively. Anesthesiologists (18%) were significantly less likely to suspend DNR orders than surgeons (38%) or internists (34%)..
The two disorders occasionally have overlapping manifestations and diagnostic confusion can result. Here is a case report and review illustrating, among other points, that cardiac sarcoidosis can manifest epsilon waves.
This two part review is not everything you need to know but it's a nice overview and a reference you'll want to have handy.
Part 1
Part 2
There is an emerging debate about normal saline inducing metabolic acidosis and increasing the risk for renal injury, with a resulting shift toward the use of ringers lactate. The latter, however, in large volumes, may be associated with hyponatremia and its consequences. Ringers acetate is posited as the ideal “balanced crystalloid” in terms of both acid-base status and tonicity. Recent review here. High level trials are needed.
A recently published article summarizes the evidence and suggests approaches to management. Reviews of this type start with the presupposition that a certain level of glycemic control is desirable in hospitalized patients. Unfortunately though, at least for non surgical patients, evidence in favor of any particular target is lacking.
Absent such evidence let's start with what we know. We know we don't want patients in the hospital to slip into DKA or a hyperosmolar state, or to develop fluid and electrolyte disturbances as a result of marked hyperglycemia. On the other extreme we don't want them hypoglycemic. Is anything and everything in between those extremes OK? Probably not, but without evidence based targets what should we do? We can do little more than arbitrarily choose regimens based on what seems “reasonable” according to clinical expertise.
For critically ill patients an insulin drip affords flexibility of titration and reliability of drug delivery as opposed to the erratic sub Q absorption that might occur if the patient is in shock. I have posted extensively on glycemic control in critical illness in previous posts [1] [2] [3] and will not elaborate further here.
For the non critically ill setting we have some data on surgical patients:
RESEARCH DESIGN AND METHODS This randomized multicenter trial compared the safety and efficacy of a basal-bolus insulin regimen with glargine once daily and glulisine before meals (n = 104) to sliding scale regular insulin (SSI) four times daily (n = 107) in patients with type 2 diabetes mellitus undergoing general surgery. Outcomes included differences in daily blood glucose (BG) and a composite of postoperative complications including wound infection, pneumonia, bacteremia, and respiratory and acute renal failure.
RESULTS The mean daily glucose concentration after the 1st day of basal-bolus insulin and SSI was 145 ± 32 mg/dL and 172 ± 47 mg/dL, respectively (P less than 0.01). Glucose readings less than140 mg/dL were recorded in 55% of patients in basal-bolus and 31% in the SSI group (P less than 0.001). There were reductions with basal-bolus as compared with SSI in the composite outcome [24.3 and 8.6%; odds ratio 3.39 (95% CI 1.50–7.65); P = 0.003]. Glucose less than 70 mg/dL was reported in 23.1% of patients in the basal-bolus group and 4.7% in the SSI group (P less than 0.001), but there were no significant differences in the frequency of BG less than 40 mg/dL between groups (P = 0.057).
CONCLUSIONS Basal-bolus treatment with glargine once daily plus glulisine before meals improved glycemic control and reduced hospital complications compared with SSI in general surgery patients. Our study indicates that a basal-bolus insulin regimen is preferred over SSI in the hospital management of general surgery patients with type 2 diabetes.
This study only compared two insulin strategies. It did not evaluate particular glycemic targets. A similar study on non sugical ward patients was done by the same investigators but it addressed only the surrogate outcome of glycemic control, not whether better control was associated with improvement in meaningful clinical outcomes.
Both studies showed that a basal-bolus regimen provided tighter glycemic control than did a simple sliding scale when the latter was used as the sole modality.
So for ward patients we can summarize it this way:
Optimal glycemic targets are unknown.
Basal-bolus regimens provide better glycemic control than sliding scale (SSI) as the sole modality.
Basal-bolus regimens are associated with better clinical outcomes than SSI in surgical patients.
It is not known whether basal-bolus insulin provides better clinical outcomes in medical patients.
With next to no evidence to go on the guidelines are based on physiologic rationale and expert opinion. The review cites the guidelines and proposes an algorithm.
A few practical points from the review:
Sliding scale coverage is discouraged by the authors but may be acceptable for short hospital stays in which it is anticipated that the patient will be NPO for a significant period of time.
What to do with oral agents is a matter for clinical judgment but the authors offer some cautions:
We tend to avoid the use of oral antihyperglycemic agents. Sulfonylureas may lead to hypoglycemia if nutrition is interrupted. There is no inherent reason that metformin could not be used, but given its risk for lactic acidosis and the frequent complicating features of hospitalized patients that might increase this risk (renal failure, dehydration, severe heart failure, acidosis), it would appear best to avoid this medication. Thiazolidinediones can be continued if there are no concerns of heart failure, although an interruption in therapy of a few days should not appreciably alter glucose levels. Incretin-based therapies (DPP-4 inhibitors and GLP-1 receptor agonists) are ideally used in patients who are eating because they target mainly postprandial glucose and so should probably be avoided when nutritional intake is forbidden or tentative. GLP-1 receptor agonists may also result in nausea so are best avoided in this setting. Some experts have proposed that, because these drug classes are not associated with hypoglycemia and because their activity appears to be in part related to the degree of hyperglycemia, they may have a role in acutely ill patients. Adequately powered, randomized clinical trials will be needed.
Finally the authors address discharge planning and emphasize the need for preparations to begin 2-3 days in advance if possible. Transitioning to post-hospital diabetes care is difficult for the hospitalist, who will not be managing the patient as an outpatient.
HT to Hospital Medicine Virtual Journal Club.
From a recent paper:
Patients with hypogammaglobulinemia who do not fulfill all the classical diagnostic criteria for common variable immunodeficiency (reduction of two immunoglobulin isotypes and a reduced response to vaccination) constitute a diagnostic and therapeutic dilemma..
The authors studied the two conditions and concluded:
..idiopathic primary hypogammaglobulinemia patients who do not fulfill all diagnostic criteria of common variable immunodeficiency have moderately decreased immunoglobulin levels and often a normal peripheral B-cell subset distribution, but still suffer from serious infectious complications.
They did not, however, exhibit the non infectious complications seen in common variable immunodeficiency.
In appropriately selected patients high precordial lead placement (V1 and V2) may increase the sensitivity for detection of Brugada patterns. It also decreases the specificity and inadvertent high placement could lead to an unwarranted diagnosis of Brugada syndrome.
A 55% increase in all cause mortality. AJC paper here.
A series of talks on resuscitation and critical care medicine from various past conferences.
The association was strong in this study.
The debate on the cardiac risks from NSAIDs has shifted. Quite a few years ago when Vioxx was yanked (yeah, remember Vioxx, the target of all the trial lawyer ads?) the word was that it was uniquely risky for cardiac events. In the ensuing years I followed the related literature closely and wrote many posts debunking that claim. And more here: [1] [2] [3]
In considering the multiple studies cited in those posts my take was that all the NSAIDs are dangerous, the older ones as much as the COX-2s. The common thread was that naproxen was the least harmful but still harmful.
So the other day I came across this post which points to a recent meta-analysis suggesting that naproxen is not associated with cardiovascular risk. From the meta-analysis:
The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs. Although NSAIDs increase vascular and gastrointestinal risks, the size of these risks can be predicted, which could help guide clinical decision making.
In terms of major vascular events the RR for naproxen was 0.93 (0.69-1.27).
The post comes just short of saying naproxen is safe and concludes:
If you can, avoid NSAIDs in patients with cardiac risk factors. Ibuprofen isn’t a safe alternative. If you need to give an NSAID for whatever reason, use naproxen and use short courses of therapy.
There are two pieces missing from the discussion:
Consider nonacetylated salicylates
That's what this patient information page from the American Heart Association suggests, but it is seldom discussed.
Cardiorenal risk may be more important than cardiovascular risk
As stated in the post, the absolute increase in cardiovascular risk from NSAIDs is low. The adverse cardiorenal effects of (non-salicylate) NSAIDs, though underdiscussed, are well documented. I don't know what the absolute cardiorenal risk is but I think it is much higher. In hospital medicine I see it week after week in patients with uncontrolled hypertension, heart failure exacerbations and AKI. Naproxen is NOT exempt form this. Note that in the meta-analysis cited above it was associated with nearly double the risk of heart failure. Heart failure due to NSAIDs is a cardiorenal phenomenon.
The current state of the art, according to a recent review:
Recent findings: A general consensus exists on the beneficial prophylactic effect of hydration. This seems to act by increasing urine flow rate and, thereby, by limiting the time of contact between the contrast media and the epithelial tubular cells. On the contrary, both observational trials and randomized studies are often controversial in their conclusions on the efficacy of several drugs tested to prevent CI-AKI. Compounds evaluated include diuretics (furosemide), antioxidants (i.e., N-acetylcysteine and statins), and vasodilators (i.e., calcium antagonists, dopamine, and fenoldopam). Due to the negative and/or controversial clinical results, none of these drugs has been currently recommended to prevent CI-AKI.
This is an excellent review in Chest covering not only fever but the various hyperthermia syndromes. It contains a lot of pearls.
I enjoy reading about medicine's great mentors and just found this tribute to Henry J. L. (Barney) Marriott. Marriott, who passed away several years ago, was a renowned teacher of electrocardiography. I attended many of his workshops over the years. I have kept some of the notes and handouts and may post some of Barney's electrocardiography pearls here from time to time.
In this as in other studies the mutation is associated with increased rates of thrombosis as well as other complications.
The topic was recently reviewed here. The waning role of beta blockers is due to the changing profile of the MI patient. The current profile of the post MI patient differs from the profile of the MI patient of the 80s. From the review:
Purpose of review: This review will assess whether the 25-year-old evidence base to support routine prescribing of β-blockers after myocardial infarction (MI) is relevant to modern management.
Recent findings: The evidence base to support the recommendation for the widespread use of β-blockers after MI was near-finalized in the mid-1980s. Whereas the use of intravenous β-blockers is waning, the routine use of oral β-blockers after MI is still regarded as evidence based. In the past 25 years, the introduction of coronary reperfusion and of effective nonreperfusion therapies has changed the natural history of MI and there have been substantial changes in the definition of MI. The relevance of old clinical trial data collected in patients who bear little resemblance to today's MI patients is questioned. Recent analyses have shown that there is no convincing evidence for the use of β-blockers as first-line therapy in hypertension or in patients with stable coronary heart disease. In contrast, the evidence base for the use of β-blockers in heart failure is strong and contemporary.
Summary: A rational recommendation for the modern treatment of MI would be to limit the use of β-blockers in the post-MI patient to higher-risk patients with evidence of ongoing ischemia, heart failure, or left ventricular dysfunction. There is no evidence to support the routine use of oral β-blockers in low-risk MI patients.
Epidemiologic evidence suggests a healthy life style may help.
Traditionaly we are used to thinking of two varieties: discoid lupus (DLE) and subacute cutaneous lupus (SCLE). The latter is characterized by autoantibody to Ro/SSA. In recent years more has been learned about the genetics and the understanding has become more complex as reviewed here. Free full text.
The best overview I've seen, available as free full text.
Here are some interesting results from a review of echocardiography use patterns and their impact on patient care:
Importance Transthoracic echocardiography (TTE) accounts for almost half of all cardiac imaging services and is a widely available and versatile tool. Appropriate use criteria (AUC) for echocardiography were developed to improve patient care and health outcomes. Prior studies have shown that most TTEs are appropriate by AUC. However, the associations among TTE, AUC, and their clinical impact have not been well explored.
Objectives To describe the proportion of TTEs that affect clinical care in an academic medical center overall and in subgroups defined as appropriate and inappropriate by AUC.
Design and Setting Retrospective review of medical records from 535 consecutive TTEs at an academic medical center was performed. The TTEs were classified according to 2011 AUC by 2 cardiologists blinded to clinical impact and were assessed for clinical impact by 2 cardiologists blinded to AUC. Clinical impact was assigned to 1 of the following 3 categories: (1) active change in care, (2) continuation of current care, or (3) no change in care...
Results Overall, 31.8% of TTEs resulted in an active change in care; 46.9%, continuation of current care; and 21.3%, no change in care. By 2011 AUC, 91.8% of TTEs were appropriate; 4.3%, inappropriate; and 3.9%, uncertain. We detected no statistically significant difference between appropriate and inappropriate TTEs in the proportion of TTEs that led to active change in care (32.2% vs 21.7%; P = .29).
Conclusions and Relevance Although 9 in 10 TTEs were appropriate by 2011 AUC, fewer than 1 in 3 TTEs resulted in an active change in care..
A possible explanation for this discrepancy is that core measures and care pathways rather than clinical judgment are driving test ordering.
This is not practice changing but interesting:
Objective To study the effectiveness and safety of intensive glucose management in patients with ACS who have hyperglycemia, aiming at strict blood glucose normalization...
Patients with ACS with an admission plasma glucose level of 140 to 288 mg/dL were eligible for inclusion and enrolled from July 23, 2008, to February 8, 2012. Patients with insulin-dependent diabetes mellitus were excluded.
By insulin-dependent I'm not sure if they meant DM type 1 or patients with DM 2 who were on insulin for glycemic control. Anyway, here's more from the paper:
Interventions Intensive glucose management strategy, aiming at a plasma glucose level of 85 to 110 mg/dL by using intravenous insulin, or to conventional expectative glucose management...
Main Outcomes and Measures End points were assessed according to the intention-to-treat principle. The primary end point was high-sensitivity troponin T value 72 hours after admission (hsTropT72); secondary end points, area under the curve of creatine kinase, myocardial band (AUC–CK-MB), release and myocardial perfusion scintigraphy findings at 6 weeks’ follow-up.
Results In the intensive management arm, median hsTropT72 was 1197 ng/L (25th and 75th percentiles of distribution, 541-2296 ng/L) vs 1354 ng/L (530-3057 ng/L) in the conventional arm (P = .41). Median AUC–CK-MB was 2372 U/L (1242-5004 U/L) vs 3171 U/L (1620-5337 U/L) (P = .18). The difference in median extent of myocardial injury measured by myocardial perfusion scintigraphy was not significant (2% vs 4%) (P = .07). Severe hypoglycemia (less than 50 mg/dL) was rare and occurred in 13 patients. Before discharge, death or a spontaneous second myocardial infarction occurred in 8 patients (5.7%) vs 1 (0.7%) (P = .04).
Conclusions and Relevance Intensive glucose regulation did not reduce infarct size in hyperglycemic patients with ACS treated with PCI, and was associated with harm.
The glycemic target of the treatment group, 85-110 mg/dl, is one we would never use today in hospitalized patients. It has been shown over and over again that in hospitalized patients with a variety of conditions such intensity of control is not beneficial and probably harmful. Neither should we ignore hyperglycemia. The problem is we do not know the optimal level. We have a lot of research looking at these very strict targets. We need more evidence about more relaxed control targets.
This essay on auscultation opens with:
Years ago I heard a story about a sage practitioner who was making teaching rounds. The house staff watched as he listened to the patient's heart with his stethoscope for perhaps 5 minutes. He then stood up to stretch his back and a resident asked him what he thought about the heart murmur. The practitioner responded, “What murmur? I'm still listening to the first heart sound.”
From back in the day when the stethoscope was a clinical tool instead of a coding tool.
A recent run through on this topic at ERCAST has some nice pearls on the nuances of wide gap acidosis.
We're all familiar with the mnemonic MUDPILES for the differential diagnosis. So, first, what does it stand for? (There are a few variations on this).
M-methanol (I would add medications, e.g. metformin).
U-Uremia
D-DKA (which should also remind you of AKA, alcoholic ketoacidosis).
P-propylene glycol
I-infection, iron, INH, inborn errors of metabolism
L-lactate
E-ethylene glycol
S-salicylates
I haven't found it all that helpful but there it is. And as the discussants at ERCAST point out it's not all that simple. Here are a few pearls from the discussion:
Toxic alcohols
We routinely check the osmolar gap but it's not as straightforward as we'd like. It's elevated early in the course but goes away as the parent compound is metabolized. Toxic acids are generated by this metabolism and by the time metabolic acidosis is seen the osmolar gap may have closed.
Check an ethanol level because it figures into the osmolar gap calculation. Also, an ethanol level over 100 makes it less likely (though doesn't rule out) that a toxic alcohol ingestion is responsible for the acidosis. The common sense reason for this is that significant ethanol on board makes it less likely that the patient would have sought an alcohol substitute. Moreover, ethanol inhibits the metabolism of toxic alcohols (it was an antidote before we had fomepizole). So if a significant amount of ETOH was ingested before the toxic alcohol (enough to give an ETOH level of over 100) it would protect against the development of acidosis.
The metabolic acidosis induced by toxic alcohol ingestion can be profound, so think of toxic alcohol when you see single digit bicarbs. This is a soft clue, not an absolute rule.
Don't forget to consider propylene glycol as a cause of toxic alcohol related acidosis. Though we are used to thinking of it only in hospitalized patients getting large doses of certain medications (see here) remember that it is contained in “pet friendly” antifreeze.
Hypocalcemia (or a rapid, unexplained downward trend in the serum calcium) is a surrogate marker and may offer a clue for ethylene glycol intoxication.
Ketoacidosis: is it diabetic ketoacidosis (DKA) or alcoholic ketoacidosis (AKA)?
The history and clinical circumstances usually make this distinction clear. When they don't, there are clues. First, if your hospital lab can measure both ketone bodies the ratio of beta hydroxy butyrate to acetoacetate may be helpful, as it tends to be higher in AKA due to the profound redox shift that prevails in that condition. In addition, simple volume repletion and dextrose (or food) will generally correct AKA quickly, in a matter of a few hours. (What the podcast didn't mention is the need to give thiamine before food or dextrose in alcoholic patients).
Lactic acidosis: remember the confounders
Elevated lactate levels may accompany other disturbances and not be the principal (or original) cause of the acidosis. For example, one of the metabolites of ethylene glycol causes a falsely elevated lactate due to a lab artifact. Propylene glycol is actually metabolized to lactate, leading to a real lactic acidosis. Lactic acidosis accompanies salicylate intoxication since salicylate in toxic doses is a mitochondrial poison, uncoupling oxidative phosphorylation.
According to this report it seems to be an emerging infection, at least in European countries.
Time in therapeutic range (TTR) is important for the effectiveness and safety of warfarin. TTR has been found to be poor in recent studies which in part explains the favorable profile of target specific oral anticoagulants in comparison to warfarin.
It was hoped early on that genomic testing to guide dosing would have a favorable impact on TTR and hence clinical effectiveness. But when subjected to the scrutiny of clinical investigation the field has been controversial if not disappointing.
Two recent studies recently published in NEJM [1] [2] have conflicting results and hence will do little to resolve the controversy. TTR as a whole in these studies was poor.
There is a strong association in several forms of vasculitis. This review is available as free full text. Here are some key points from the abstract:
Increasing evidence supports the use of immunosuppression in the management of venous thrombosis in Behçet's disease. An increased incidence of thromboembolic disease in antineutrophil cytoplasmic antibody-associated vasculitis has been recognized, especially during periods of active disease. In addition, a higher risk of ischemic heart disease in these patients has also been observed. As in giant cell arteritis, recent evidence supports the role of aspirin in the prevention of ischemic events in Takayasu's disease.
Here is a formula and on line calculator from Dr. Smith's ECG blog. The page also has a link to the primary source of the original research behind the formula. The QT interval factors in, as STEMI tends to lengthen the QT interval. It is important to note that the formula is intended for use in subtle cases (reflecting the population studied in the original research) and should not be applied in cases where STEMI is obvious. Moreover the formula is not reliable if there is electrocardiographic LVH.
From a recent review:
There is little evidence from large multicenter trials to direct fluid therapy in patients at risk of acute kidney injury (AKI). Evidence of benefit for fluid administration from single center studies of fluid resuscitation to hemodynamic goals needs to be weighed against evidence of harm associated with fluid overload in large observational studies. The composition of intravenous fluid may affect the risk of AKI. Even latest-generation hydroxyethyl starches increase the risk of severe AKI in general and septic ICU patients. Isotonic saline has been associated with greater incidence of AKI in comparison to buffered crystalloids. Experimentally, infusion of saline results in reduction in renal perfusion in comparison to buffered solutions.
Summary
Clinicians need to weigh the balance between adequate resuscitation of cardiac output and avoidance of fluid overload. Protocolized resuscitation to hemodynamic goals may help achieve these conflicting goals at least in the early phases of critical illness. In critically ill patients with, or at risk of, AKI, clinicians should avoid starch and, possibly, saline solutions.
Here's a brief topic discussion at Emegency Medicine Pharm D. The evidence favoring this is quite weak but, as cited in the post, IV mag is endorsed in this review published about a year ago in Circulation. Concerning the management of shivering and general discomfort it recommends:
All patients receiving TH should receive low-dose, continuous infusions of both a sedative and an analgesic agent to prevent any potentially painful sensation or discomfort and to suppress shivering. Preference should be given to agents with short half-lives (eg, propofol or midazolam for sedatives and fentanyl or hydromorphone for analgesia)...
Magnesium sulfate may raise the shivering threshold, so we give an initial 4-g bolus to all patients receiving TH.15 If shivering persists, rapid uptitration of anesthetics with analgesic boluses is effective, although some patients require NMBAs to completely suppress shivering. We have found that selective use of NMBA boluses (3 doses of cisatracurium 0.15 mg/kg IV every 10 minutes) is often effective and allows patients to achieve target temperature without a continuous NMBA infusion. Some centers use continuous NMBAs in all patients during the entire TH process; others limit NMBA infusion to just the initiation period.
Though the hereditary nature of AAA has long been known the genetics are just now being worked out. The recent evidence is summarized in this review.
Physiologic rational and low level evidence point to reduced VILI if low tidal volumes are used, for any indication. This has not been subject to rigorous systematic study, however, and there is concern for unintended consequences, such as greater need for sedation, and the potential for ventilator dyssynchrony. Clinical judgment should ultimately prevail pending high level trials. From a recent review:
Successive preclinical studies almost without exception show that ventilation with lower tidal volumes reduces the injurious effects of ventilation in animals with uninjured lungs. This finding is in line with results from recent trials in ICU patients without ARDS, demonstrating that ventilation with lower tidal volumes has a strong potential to prevent development of pulmonary complications and maybe even to improve survival. However, evidence mostly comes from nonrandomized clinical trials, and concerns are expressed regarding unselected use of lower tidal volumes in the ICU, that is, in all ventilated critically ill patients, since this strategy could also increase needs for sedation and/or neuromuscular blockade, and maybe even cause respiratory muscle fatigue. These all then could in fact worsen outcome, possibly counteracting the beneficial effects of ventilation with lower tidal volumes.
According to this review there are multiple mechanisms, including reducing the inflammatory burden of dysfunctional visceral adipose tissue.
According to the description of the site the aim is to make biology easier and fun.
A great resource is located here at the American College of Medical Toxicology web site. A related post at Academic Life in Emergency Medicine elaborates on some of the key points.
Involve nephrology and poison control early.
Volume depletion in the salicylate intoxicated patient can be taken for granted. Replete appropriately.
Know the indications for hemodialysis.
Maintain alkalemia (pH 7.50-7.55) and alkaline urine pH.
These measures keep salicylate out of the CNS and enhance renal excretion, respectively.
Intubate if you must but be aware of, and prepared for, the hazzards.
Remember the goal of alkalemia. Neither the person bagging a sedated or paralyzed patient nor the mechanical ventilator can do as reliable a job of hyperventilation (to preserve a normal, or better yet, alkaline, serum pH) as can the brain of an awake patient. The pH may fall precipitously around the time of intubation resulting in a sudden influx of salicylate into the CNS, which can be catastrophic.
Resources for EM trainees.
A recent study found that application of a care bundle of evidence based processes reduced mortality. The bundle consisted of:
Six aspects of clinical management from 16 articles showing an impact on outcome were selected as QCIs (Table 2): performance of follow-up blood cultures; early source control; performance of echocardiography in patients with specific criteria; early use of intravenous cloxacillin in cases of methicillin-susceptible S. aureus (MSSA) (or cefazolin in patients under hemodialysis) as definitive therapy in nonallergic patients; adjustment of vancomycin dose according to trough levels; and provision of an appropriate duration of therapy according to the complexity of infection.
This confirms that treatment of staph aureus bacteremia is complex and multifaceted, and that adherence to several care processes is important for a good outcome. That is why ID consultation has been demonstrated to produce better outcomes as I noted back in 2009. From that post:
So if ID consultation really is producing better outcomes what are the ID docs adding? From the descriptions above, better evaluation and management all the way around, it would appear. Based on the descriptions above, if ID consultation is not readily available at your hospital, be aware of the modalities often overlooked by non-specialists: knowing when vanco is not enough; getting follow up blood cultures; source control; treating long enough; appropriate use of imaging to diagnose endocarditis and other complications; switching to a beta lactam antibiotic if the organism turns out to be MSSA.
This review summarizes its limited adjunctive role:
MgSO4 has a role in severe exacerbations of acute asthma and there is no evidence of benefit outside this clinical situation. Both nebulized and i.v. treatments are well tolerated and inexpensive. In adults, the most effective route of administration is i.v. There are no direct comparison studies in children. Further research should focus on more severe exacerbations.
When you get a call that your patient just spiked a fever there's an immediate disconnect. The nurse wants you to “order something for it” (meaning a medication such as Tylenol to bring it down) while you are immediately thinking etiology (Has the patient acquired an infection? Do I need to get cultures and an xray stat?). The nurse wants an order for an antipyretic. That's not at the top of your list. You may even feel you're being maneuvered into ordering something that could be harmful. That's when you need to be armed with the evidence.
I while back I reviewed this topic in a couple of posts [1] [2]. More recently Mill Hill Ave Command addressed the topic and I thought it would be a good time to revisit it here. The general conclusion of the Mill Hill Command post was that lowering of body temperature with antipyretics or via external means is not supported by evidence. I agree although as I pointed out in my previous posts the exceptions must be kept in mind: hyperthermia syndromes and heat stroke, acute cerebrovascular disease and coma post cardiac arrest. As I also pointed out there was one study showing benefit from external cooling (not antipyretics!) in patients with septic shock on pressors, in terms of decreased pressor requirement and decreased mortality. That is just one study with methodologic concerns and the findings need to be replicated.
There may be other exceptions where physiologic rationale and clinical judgment suggest the use of antipyretics, e.g. fever driving tachycardia in a patient with heart failure or myocardial ischemia, though not supported by high level evidence.
Finally, since my original posts there has been a point-counterpoint with rebuttals published in Chest. It's an interesting exchange that probes the literature on both sides. I think the naysayers won the debate.
